Bufadienolides from parotoid gland secretions of Cuban toad Peltophryne fustiger (Bufonidae): Inhibition of human kidney Na(+)/K(+)-ATPase activity.

Parotoid gland secretions of toad species are a vast reservoir of bioactive molecules with a wide range of biological properties. Herein, for the first time, it is described the isolation by preparative reversed-phase HPLC and the structure elucidation by NMR spectroscopy and/or mass spectrometry of nine major bufadienolides from parotoid gland secretions of the Cuban endemic toad Peltophryne fustiger: ψ-bufarenogin, gamabufotalin, bufarenogin, arenobufagin, 3-(N-suberoylargininyl) marinobufagin, bufotalinin, telocinobufagin, marinobufagin and bufalin. In addition, the secretion was analyzed by UPLC-MS/MS which also allowed the identification of azelayl arginine.

Inhibitory effect of combinations of digoxin and endogenous cardiotonic steroids on Na+/K+-ATPase activity in human kidney membrane preparation.

Aims: Cardiac glycosides have been extensively used in the treatment of congestive heart failure for more than 200 years. Recently, cardenolides and bufadienolides were isolated from mammalian tissue and are considered as a new class of steroidal hormones. The aim of the present work was to characterize the interaction between the most clinical used cardiac glycoside digoxin and the cardiac glycosides known to exist endogenously, i.

Insights into the mechanism of Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan.

The molecular mechanisms involved in Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan were investigated. We show that this compound decreases the free sulfydryl groups present in the enzyme and that its inhibitory effect is prevented by dithiothreitol and other two sulfydryl containing reagents. We propose a redox cycle culminating with the irreversible oxidation of sulfydryl groups essential for the catalytic activity of this enzyme and of two other related P-type ATPases.

Synergistic interaction between ouabain and 8-methoxy-3,9-dihydroxy coumestan, a non-steroidal synthetic inhibitor of Na+,K+-ATPase.

The use of combination drugs is very common in therapeutics as in the treatment of infectious diseases, cancer and heart failure but controversies about analysis of these interactions are frequent. The aim of the present work was to characterize the interaction between ouabain and 8-methoxy-3,9-dihydroxy coumestan (LQB93), a non-steroidal synthetic inhibitor of Na+,K+-ATPase, as well as the interaction between ouabain and ouabagenin, two cardiac glycosides sharing the same binding site. Inhibition of rat kidney Na+,K+-ATPase with increasing concentrations of the drugs alone or of mixtures of ouabain:ouabagenin and LQB93:ouabain in a fixed 1:4 ratio was performed.